Over time, many important discoveries have revolutionized the practice of medicine. The discovery of penicillin and other antibiotics for instance, have changed the ways infectious diseases are treated and the discovery of X-rays has introduced new ways for diagnostics. Methadone could have occupied a similar position but for the stigma and discrimination that drug use disorder and opiate use suffer from.
The 21st century saw Malaysia leading the pact of countries with a most rapidly rising HIV epidemic. After tireless efforts by individuals and organizations, MMT was finally instituted in the country. The program is now implemented at public and private health facilities and other facilities involved with drug use communities. The primary goal is to blunt the rapid rise in HIV infections although the public mainly see it as a treatment for drug addiction. This paper reports a finding from a pilot project on MMT in a small cohort of injecting drug users in SAHABAT and Klinik Dr Khafiz. It is intended to provide a basis for a more comprehensive research to understand factors that can contribute to successes with MMT as, among heroin drug users, MMT has demonstrated effectiveness in reducing HIV risk behaviors and HIV infection [12–14]. MMT programs in Malaysia are implemented in government hospitals as well as in private practice.
SAHABAT is a non-governmental organisation working for and with drug use communities in Kelantan. MMT was introduced in SAHABAT in 2008. SAHABAT is the first centre in Malaysia to have both the MMT program and NSEP running under one roof. SAHABAT also boasts as the only NGO-run centre that was allowed to prescribe methadone. The other centre included in this study was Klinik Dr Khafiz, a general practice clinic near Kuala Lumpur. It was included to provide an insight of MMT practice in the community.
In this study, all the patients enrolled were males in the productive age group. This underscores the importance of proper management of opiate addiction because of its potential influence on population growth, demography as well as productivity of the nation as young males play a significant role in providing Malaysia's work force. Of note was a high prevalence of HIV positivity. In most countries that practice harm reduction among injecting drug users, the incidence of HIV positivity is generally 1-2% . The high prevalence seen in our Malaysian cohort suggests the need for urgent effective measure to control. This is now done in Malaysia with MMT and NSEP.
Drug use disorder is a chronic relapsing disease. Our study revealed that no age group is spared. Our youngest patient was 20 years-old. They began their drug habit as early as when they were 12 years. The oldest patient was 56 years and the oldest age a patient started with the habit was 32 years. The duration of illness among our patients ranged from two years to 38 years and averaged 13 years. These have implications. For one, preventive measures for drug use disorder must begin early and should be continued through all ages. Patients afflicted with the disease should also have long follow ups as they evidently continue with their habits right through their golden years. The longer they continue on the habit, the greater is the chance for them to contract diseases like HIV, if they have not yet been infected. Being young and otherwise healthy, young addicts may find themselves constrained in various activities and this may lead them to many other unhealthy practices.
Drug users do not live in isolation. Apart from transmission through the sharing of injection equipments, having the HIV reservoir, drug users can also transmit the disease to their sexual partners, through penetrative sex. Thus, what started in Malaysia as a concentrated epidemic among drug users is now showing evidence for a more generalized epidemic through sexual transmission. In the beginning, less than one percent of HIV victims were females. Now it stands at about 20% and this clearly demonstrates the generalization of the HIV epidemic in Malaysia. Most of the afflicted females are also wives and spouses of drug users who are themselves HIV positive and not sex workers as many would have expected. There is however evidence for a growing epidemic among sex workers and this again has the potential to generalize into the community.
A most important characteristic of a good MMT program is high retention rate . Our overall retention rate at 6 months was low. Coupled with the relatively small percentage of opiate-dependent individuals having access to MMT in Malaysia, this may threaten the success of MMT as a tool to reduce HIV spread in Malaysia. The low retention rate we saw was probably due to the low daily maintenance dose of methadone our patients got. Our daily doses averaged 57 mg. Its median was lower at 50 mg. Our results revealed that best retention rates were obtained among patients treated with 80 mg or more methadone per day. In parallel, our patients treated with 80 mg or more methadone per day showed the least tendency for re-injecting. It is therefore interesting to note that, despite claims by many physicians that relatively lower doses of methadone would be sufficient for our Malaysian patients, our results showed otherwise.
Our findings were also in parallel with studies that showed a sufficiently high dose was required for improved outcomes . High doses suppress illicit heroin use and improve retention and outcomes [38, 39]. Dole's original research discovered that 80 to 120 milligrams of methadone per day, on average, was an effective dose. Dozens of studies since then have demonstrated that dosing in that range resulted in superior treatment outcomes, such as better retention of patients in treatment and less illicit drug use [9, 11, 39]. Patients maintained on inadequately low doses are much more likely to use illicit opioids and respond poorly to therapy . A study by Strain et al  also concluded that patients receiving 80 mg or more methadone per day had significantly greater decreases in illicit opiod use. Another study concluded that a sufficiently high dose of substitution therapy was required for improved outcome  and many other independent studies also showed that high doses of methadone were significantly more effective in suppressing illicit heroin use and in retaining patients in the treatment [38, 41, 42].
Inadequate doses and premature termination will probably be the greatest threats to a successful MMT program in Malaysia. Malaysian doctors tend to use low doses despite the fact that the traditional dosing with lower doses are expected to be ineffective . Many also actively encourage their patients to terminate MMT early. They may outwardly say that they use lower methadone doses because of fear for ethnic difference that would put patients at risks for toxicity. They will not admit their fears with methadone (and all opiates actually!) just for the simple reason that methadone is an opiate, just like heroin and morphine!. Malaysian doctors are not alone in this. Despite evidence for the need for a daily dose of 80 mg to 100 mg, most patients are maintained on much less. It is probably understandable that the lay public may not understand the scientific basis for MMT and could be disparaging and become critical of it. It is however less clear why many physicians and other health care providers have the same views. Most have actually received clear information on the principles underlying MMT. They may also claim that they want to prescribe as few medications as possible but this sounds hollow. Many frequently easily prescribe other mood altering drugs, such as the benzodiazepines that can also produce psychologic and physiologic dependency. Even if they claim they fear adverse effects, the adverse, physiologic effects of MMT are minimal and methadone is probably associated with the least side effects of any drug in a physician's pharmacologic armamentarium, when used appropriately. Illicit use of benzodiazepines, even among MMT patients, are now threatening to derail the MMT program as many continue to inject benzodiazepines although they may have discontinued injecting opiates. There is probably a general "opiophobias". It is known that some doctors even hesitate to use opiates even when indications are clear. Efforts should therefore be made urgently to reeducate these doctors. In their hands is the future of the nation. Their failure to prescribe adequate methadone doses will lead to therapeutic failure for MMT and this has dire consequences.
Our physicians justify the lower methadone doses used on account of the smaller body sizes of their  and the possibility of reduced drug metabolisms . However, drug metabolism and drug doses do not depend on the body weight alone. It is more likely to be related to the expression level and catalytic activity of the putative drug metabolising enzymes (DME) in the individual patients . With methadone, metabolism is complex, mediated by several polymorphic DMEs as reflected by the large variability observed with methadone disposition and half lives [29–31]. DME polymorphisms have large geographic and ethnic variations . With CYP2B6 and CYP3A4, two enzymes that have been implicated in methadone metabolism, the ethnic groups in Malaysia show polymorphism with types and frequencies that differed from each other and from ethnic groups in other geographic location . Furthermore, the frequencies for mutations at CYP3A4 locus were found to be higher among Malay opiate dependent individuals compared to non-opiate dependent Malays. CYP3A4 is an enzyme whose activity is also altered by environmental factors like char-broiled food and grape fruits . All these would probably have more impact on methadone dose requirements in Malaysia than would body weights.
Nevertheless, as with many drugs, the dosing of methadone must be individualised . Too low a dose will lead to relapse and failure whereas too high a dose will lead to toxicity such as prolongation of QT interval and subsequent fatal polymorphic ventricular fibrillation . For some reasons such as, pharmacologic variability at the enzyme and receptor levels, high tolerance to opioids, physical condition, mental status, concurrent medications, or prior use of high-purity heroin, however, some patients require much higher daily methadone doses for treatment success, sometimes exceeding 200 mg/day or more [10, 11, 44].